U.S. patent application number 12/848435 was filed with the patent office on 2011-08-04 for method for improved scaling of filters.
This patent application is currently assigned to MILLIPORE CORPORATION. Invention is credited to Mark Blanchard, Sal Giglia, Kevin Rautio.
Application Number | 20110185552 12/848435 |
Document ID | / |
Family ID | 43037012 |
Filed Date | 2011-08-04 |
United States Patent
Application |
20110185552 |
Kind Code |
A1 |
Giglia; Sal ; et
al. |
August 4, 2011 |
Method For Improved Scaling Of Filters
Abstract
Method of reducing performance variability of membrane scaling
devices. Scaling device performance uncertainty is reduced, thereby
reducing the scaling safety factor, by specifying a narrow range or
subset of the set of all qualified manufactured membranes for
installation into scaling devices. In certain embodiments, the
scalability factor is reduced by determining where within the
performance distribution a particular membrane lies, and adjusting
the scaling factor accordingly.
Inventors: |
Giglia; Sal; (Billerica,
MA) ; Rautio; Kevin; (Billerica, MA) ;
Blanchard; Mark; (Billerica, MA) |
Assignee: |
MILLIPORE CORPORATION
Billerica
MA
|
Family ID: |
43037012 |
Appl. No.: |
12/848435 |
Filed: |
August 2, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61274142 |
Aug 13, 2009 |
|
|
|
Current U.S.
Class: |
29/407.1 |
Current CPC
Class: |
B01D 69/02 20130101;
B01D 2325/20 20130101; Y10T 29/49604 20150115; Y10T 29/4978
20150115; B01D 65/10 20130101; Y10T 29/496 20150115; G01N 15/0826
20130101 |
Class at
Publication: |
29/407.1 |
International
Class: |
B01D 65/00 20060101
B01D065/00 |
Claims
1. A method of reducing performance variability in a filtration
scaling device used to estimate the requirements of a full scale
filtration device, the method comprising: a. determining the
performance distribution of a plurality of membranes or filtration
media; b. selecting a subset of said distribution, said subset
having a known range of performance with said distribution; c.
inserting membrane or filtration media from said subset into said
filtration scaling device; and d. assigning a scaling safety factor
to said filtration scaling device, wherein said scaling factor is
directly proportional to the product of the full scale device high
end potential performance within said distribution and the scaling
device high end potential performance within said subset of said
distribution, and inversely proportional to the product of the
scaling device low end potential performance within said subset of
said distribution and the full scale device low end potential
performance within said distribution.
2. The method of claim 1, wherein said subset of membranes is a
single membrane.
3. The method of claim 1, wherein said scaling factor is the
product of the full scale device high end potential performance
within said distribution and the scaling device high end potential
performance within said subset of said distribution, divided by the
product of the scaling device low end potential performance within
said subset of said distribution and the full scale device low end
potential performance within said distribution.
Description
[0001] This application claims priority of U.S. Provisional
Application Ser. No. 61/274,142 filed Aug. 13, 2009, the disclosure
of which is incorporated herein by reference.
BACKGROUND
[0002] Manufacturers of filtration devices often offer small scale
sizing tools for initial evaluation of process streams and for
estimating membrane area requirements for the full scale process.
Ideally, small scale devices should contain a minimum of membrane
area or filtration media to save test fluid while also scaling
linearly with their corresponding large scale devices. However,
variability in the performance of small scale devices adds
uncertainty to the scale-up requirements, resulting in potentially
excessive sizing to guard against the possibility that the tested
small scale device(s) represented the low end of the performance
distribution.
[0003] In the case of microfiltration membrane filters, for
example, there are many factors that influence membrane
performance, including the pore size distribution, the membrane
chemistry, membrane thickness, membrane porosity, and others. While
membrane manufacturing processes are designed to control all of
these factors to maximize uniformity and consistency, there
inevitably will be some distribution within normal manufacturing
conditions for all of these variables. This membrane variability
limits device-to-device performance consistency and therefore
limits the precision to which large scale performance can be
predicted from small scale performance.
[0004] The performance of either large scale samples or small scale
filtration devices is often used to estimate the sizing
requirements of large scale devices. The use of small scale devices
for sizing provides an obvious economic advantage. For example, in
sterile filtration of biological fluids, 47 mm or 25 mm membrane
discs offer a convenient format for evaluating performance against
the discs to large scale membrane devices (e.g., cartridges
containing tens to thousands of times more area). For accurate
scale-up, the membrane in the small scale device must be
representative of the membrane in the large scale devices. However,
as in any manufacturing process, there is a finite tolerance in
acceptable performance from one lot of membranes to another. The
membrane in a scaling device could originate from anywhere within
the acceptable performance range. Accordingly, when estimating the
required sizing of full scale devices, the variability in membrane
performance must be accounted for, necessitating the use of liberal
safety factors in scaling estimates.
[0005] This can be illustrated by considering a hypothetical
distribution of membrane performances as shown in FIG. 1. In this
example, average performance (either permeability or throughput
capacity) of all membrane lots is normalized to one and the
acceptable range of performance is defined as .+-.30% of the mean.
One commonly employed approach is to use a small scale device
containing membrane randomly selected from the population, which
could perform at anywhere from 0.7 to 1.3. Similarly, a large scale
device could perform at anywhere within the same 0.7 to 1.3 range.
When scaling from a small scale to a large scale device, the
possibility that the small scale device contains high end (1.3)
membrane while the large scale device could contain low end (0.7)
membrane must be accounted for. That is, a scaling safety factor of
1.3/0.7=1.86 must be applied to ensure that the large scale device
requirements are not undersized (see FIG. 2). In this situation,
the worst case performance of the full system will be accurately
estimated. However, it is also possible that the small scale device
could contain membrane at the low end of the distribution (0.7)
while the large scale device contains high end (1.3) membrane.
Applying the same safety factor would result in a full system
performance of (1/3/0.7)/(0.7/1.3), or 3.45. The result would be a
filtration system that is oversized by a factor of 3.45. This value
is defined as the scaling factor uncertainty ratio (U.sub.sf)
according to the following formula (I):
U.sub.sf=(F.sub.h/S.sub.l)/(F.sub.l/S.sub.h)=(F.sub.h/F.sub.l)*(S.sub.h/-
S.sub.l) (1)
where F.sub.h is the full scale high end potential performance,
F.sub.l is the full scale low end potential performance, S.sub.h is
the scaling device high end potential performance, and S.sub.l is
the scaling device low end potential performance.
[0006] It therefore would be desirable to reduce the range of
scaling device performance in order to lower large scale device
requirements and save costs.
SUMMARY
[0007] The problems of the prior art have been overcome by the
present invention, which provides a method of reducing the range of
scaling device performance uncertainty. In certain embodiments,
scaling device performance uncertainty is reduced, thereby reducing
the scaling safety factor, by specifying a narrow range or subset
of the set of all qualified manufactured membranes or filtration
media for installation into scaling devices. In certain
embodiments, the scalability factor is reduced by determining where
within the performance distribution a particular membrane lies, and
adjusting the scaling factor accordingly. Reducing scaling
uncertainty results in significant cost savings, realized, for
example, by a reduction in the scale-up sizing requirements.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a graph of a hypothetical distribution of membrane
performance showing an acceptable range;
[0009] FIG. 2 is a graph of a hypothetical distribution of membrane
performance showing possible values for large and small scale
devices;
[0010] FIG. 3 is a graph of a hypothetical distribution of membrane
performance showing possible values for large and small scale
devices;
[0011] FIG. 4 is a graph of small scale device variability vs.
scaling factor uncertainty ratio; and
[0012] FIG. 5 is a graph of the water permeability distribution of
a set of pleated cartridges in accordance with Example 1.
DETAILED DESCRIPTION
[0013] Membrane manufacturing processes inherently result in some
variability in membrane properties even though materials and
process conditions are kept as constant as possible. As a result,
procedures have been instituted to classify or "rate" each batch or
roll of membranes after manufacture, based on performance. For
example, water permeability and throughput capacity tests are often
carried out such as by constructing membrane devices using
membranes from a given batch, measuring water permeability, and
challenging the devices with a solution containing particles of a
selected size and concentration to plug the membrane pores.
Throughput capacity (volume filtered) within a specified time
period, such as 10 minutes, or some flow reduction amount, such as
70% flow reduction, are measured, and relative capacity values are
obtained. The membranes from the given batch are then performance
rated based upon the results obtained. The performance of
filtration media may also be similarly characterized. Filtration
media is material that actively separates solids from a solution
and/or binds select materials in solution. Types of filter media
include: non-woven fabrics, activated carbon, activated clay,
cellulose, ceramic, cotton, diatomaceous earth, glass fiber, ion
exchange resins, metals, minerals, paper, nylon, sand, synthetic
fiber, Teflon, polyethersulfone, polyester, polypropylene,
polytetrafluoroethelyne, polyvinylidene fluoride, polyvinylidene
chloride, and polysulfone.
[0014] In certain embodiments of carrying out the methods disclosed
herein, each batch of membranes or filtration media produced is
characterized by performance, and a performance distribution is
established. From that distribution, a small subset is selected for
installation into scaling devices. By specifying only a narrow
range of the distribution for scaling devices, the uncertainty in
scaling from small scale to large scale devices (which by
definition can contain any qualified membrane or filtration media)
is minimized.
[0015] For example, if only the middle third of the distribution is
selected for small scale devices, as illustrated in FIG. 3, then
the performance of the small scale device will range from 0.9 to
1.1. Since the large scale devices will range from 0.7 to 1.3, the
scaling safety factor will be, (in accordance with equation (1),
where S.sub.h becomes the scaling device high end potential
performance within the subset of the distribution, and S.sub.l
becomes the scaling device low end potential performance within the
subset of the distribution), (1.3/0.9)/(0.7/1.1)=2.3. In this
example, this method results in about a 35% savings in scale-up
sizing requirements compared to conventional random membrane
selection used for scaling devices.
[0016] FIG. 4 shows scaling safety factor as a function of small
scale performance range for several levels of membrane variability.
The current state of the art is defined by the upper end of each
curve. The method disclosed herein allows for reduced scaling
uncertainty as illustrated by the arrows in FIG. 4.
[0017] In certain embodiments, the scalability safety factor can be
minimized by determining where, within the performance
distribution, the small scale device lies (using either a surrogate
or actual performance qualification test, for example), and then
adjusting the scaling factor to account for the specific portion of
the distribution that the scaling device came from. In this
approach, any membrane can be used in scaling devices. Information
about membrane performance is collected and the information is then
provided with the finished device. When the scaling device is
evaluated, this membrane performance data is used in determining
the scaling factor. For example, using the hypothetical
distribution in FIG. 1, assume that a specific membrane has a
performance value of 0.9. The scaling factor simply would be
(0.9/0.7)=1.3. This factor represents the adjustment for the
scaling device with respect to the low end of the full
distribution. Since the performance range of the scaling device is
well defined and known, S.sub.h and S.sub.l are the same, so
equation (1) reduces to:
U.sub.sf=F.sub.h/F.sub.l (2)
The scaling factor uncertainty ratio in this case becomes 1.3/0.7,
or 1.86, which represents a 46% reduction compared to uninformed
membrane selection.
Example 1
[0018] A key performance parameter of sterilizing grade membrane
filters is water permeability, which relates to the productivity of
the device. Water permeability is measured by supplying water to
the membrane, maintaining a pressure difference across the
membrane, and measuring the water flow rate. Permeability is
calculated according to the formula:
Lp=Q/(A*.DELTA.P)
where Lp is water permeability, A is the membrane area, and
.DELTA.P is the pressure difference across the membrane. Water
permeability is commonly expressed in units of L/(m.sup.2-hr-psi)
or LMH/psi. The water permeability was measured on a representative
set of pleated cartridges each containing about 0.5 m.sup.2 of
polyethersulfone membrane with a nominal pore size of 0.2 .mu.m. A
plot of the distribution is shown in FIG. 5. Water permeability
ranged from about 1000 LMH/psi to about 1300 LMH/psi. A subset of
the membranes contained in the entire population was selected for
installation into small scale disc devices containing 0.0034
m.sup.2 The selected subset range was restricted to membranes with
between about 1100 and 1200 LMH/psi, which constituted about half
of the entire membrane population. In accordance with equation 1,
the scaling factor uncertainty ratio using any membrane in the
population (prior art method) is (1300/1000)*(1300/1000)=1.69.
Using the method of this invention, the scaling factor uncertainty
ratio was reduced to (1300/1000)*(1200/1100)=1.42, which represents
a 16% improvement in scaling factor uncertainty and which
translates directly to a proportionally smaller sized full size
system compared to the prior art.
Example 2
[0019] From the water permeability distribution of Example 1, a
single membrane that had been characterized for water permeability
was selected from the entire population of membranes. Since the
water permeability of this membrane was known, equation 2 was
applicable and the scaling factor uncertainty ratio was
1300/1000=1.3, represents a 23% improvement in scaling factor
uncertainty compared to the prior art.
* * * * *